Coating system

ABSTRACT

The present invention provides a coating system for solid pharmaceutical dosage units, such as tablets. The coating system comprising (a) a subcoat; (b) an optional colorcoat; and (c) a polish coat. In a preferred embodiment, the present invention provides (a) a subcoat comprising (i) hydroxypropyl methylcellulose (HPMC) and (ii) a polysaccharide; (b) a colorcoat comprising (i) a colorant and (ii) a polysaccharide which may be the same as or different from the polysaccharide of the subcoat; and (c) a polish coat comprising (i) a polyethylene glycol and, optionally, (ii) a wax. Also disclosed is a method for providing gloss to a coated pharmaceutical solid dosage unit by coating a pharmaceutical core with the aforementioned polish coat.

FIELD OF THE INVENTION

[0001] The present invention relates to coating systems for solidpharmaceutical dosage units, such as tablets. The present inventionfurther relates to solid pharmaceutical dosage units coated with suchcoating systems.

BACKGROUND OF THE INVENTION

[0002] Coatings for solid pharmaceutical dosage units serve manypurposes. They act to isolate the active pharmaceutical material fromthe atmosphere, thereby inhibiting its degradation. They further act toisolate the active material from the oral mucosa during ingestion,thereby masking the taste of the pharmaceutically active materials, manyof which are foul tasting. Finally, such coatings are useful inimproving the visual appearance of the dosage units. This is desirablein view of the often raw, porous appearance of many solid dosage units,such as those produced using compression technology.

[0003] Many types of coating technology have heretofore been employed.Most are less than perfect. For instance, films produced fromhydroxypropyl methylcellulose exhibit excellent dissolution propertiesand adequately taste-mask the active material. However, the film itselfexhibits an unpleasant taste. Further, tablets coated with such filmsoften exhibit an inelegant appearance.

[0004] Sugar-based coatings are often employed in the coating oftablets. Such coatings exhibit excellent taste, taste-masking andappearance qualities. However, relative to film coatings, they are moreexpensive to produce and slower to dissolve.

OBJECTS OF THE PRESENT INVENTION

[0005] It is therefore an object of the present invention to produce acoating system for solid pharmaceutical dosage units which exhibits gooddissolution, appearance, taste and taste-masking properties.

[0006] It is further an object of the invention to produce coated solidpharmaceutical dosage units which exhibit good dissolution, appearance,taste and taste-masking properties.

[0007] It is still further an object of the present invention to providea method for improving the luster of a coated dosage unit through theapplication of a polyethylene glycol-containing polish coat.

[0008] These and other objects of the present invention will becomeapparent from the following description.

SUMMARY OF THE INVENTION

[0009] The present invention is directed to coating systems for solidpharmaceutical dosage units, such as tablets. The present invention isfurther directed to solid pharmaceutical dosage units coated with suchcoating systems.

[0010] The present invention provides a coating system comprising (a) asubcoat; (b) an optional colorcoat; and (c) a polish coat, as well assolid dosage units bearing such coatings.

[0011] In a preferred embodiment, the present invention provides (a) asubcoat comprising (i) hydroxypropyl methylcellulose (HPMC) and (ii) asugar such as a polysaccharide; (b) a colorcoat comprising (i) acolorant and (ii) a polysaccharide which may be the same as or differentfrom the polysaccharide of the subcoat; and (c) a polish coat comprising(i) a polyethylene glycol and, optionally, (ii) a wax.

[0012] In another embodiment, the present invention provides a dosageunit form comprising a medicament-containing core coated with thecoating system of the present invention.

[0013] In still another embodiment of the present invention there isprovided a method for preparing a pharmaceutical solid dosage unit bycoating a pharmaceutical core with the aforementioned coating system.

DETAILED DESCRIPTION OF THE INVENTION

[0014] The coating systems of the present invention include at least two(2) coats—a subcoat and a polish coat.

[0015] The subcoat comprises a cellulosic material capable of beinghydrated and applied as an aqueous solution through film-coatingtechnology. Such materials are well known in the art. Preferredcellulosic materials are hydroxypropyl cellulose (HPC) and hydroxypropylmethylcellulose (HPMC). Most preferred are HPMC's having molecularweights ranging from about 5,000 to about 15,000. Mixtures of suchHPMC's may also be employed. HPMC's having molecular weights of 5,000and 15,000 are referred herein as E5 and HPMC E15, respectively, and areavailable as Methocel® E5 and Methocel® E15, respectively, from DowChemical Co. of Midland, Michigan. Preferably, these HPMC's are presentin a weight ratio of HPMC E5:HPMC E15 of about 3:1 to 1:2. Mostpreferably, these HPMC's are present in a weight ratio of about 2: 1, onthe same basis.

[0016] The subcoat further contains a sugar. The use of sugars incombination with a cellulosic material is highly attractive from aneconomic point of view. For example, sucrose is approximately 50 timesless expensive than some HPMC's on a per weight basis. The sugarcomponent further acts to taste-mask the unpleasant taste normallyassociated with the cellulosic material. Useful in the practice of thepresent invention are simple sugars such as glucose, fructose andmannose and polysaccharides such as sucrose. Preferred arepolysaccharides such as sucrose. The use of sucrose is especiallypreferred.

[0017] The subcoat may also include additional materials typical inpharmaceutical coatings. These include such materials as additionalsweeteners, antioxidants, plasticizers, flavorants and combinationsthereof. In the practice of the present invention, additional materialssuch as the following are used: acesulfame-K (a sweetener marketed underthe tradename Sunett® by Hoechst Celanese Corporation of Portsmouth,Va.), propyl gallate (an antioxidant), and triacetin (a plasticizer).

[0018] The subcoat typically includes from about 40 to about 85 percentby weight of cellulosic material and from about 15 to about 60 percentby weight of the sugar component, based upon 100 percent by weight ofthe subcoat. Preferably, the subcoat includes about 50 to about 70percent by weight of cellulosic material and about 30 to about 50percent by weight of the sugar component, on the same basis. Mostpreferably, the subcoat includes about 60 to about 70 percent by weightof cellulosic material and about 30 to about 40 percent by weight of thesugar component, on the same basis. When the preferred cellulosicmaterial, HPMC, is employed, the subcoat most preferably includes about60 to about 70 percent by weight of cellulosic material and about 30 toabout 40 percent by weight of the sugar component, on the same basis.Most preferably, the subcoat comprises HPMC and sucrose in a 2:1 weightratio or 67% HPMC and 33% sucrose (on a weight basis).

[0019] The polish coat employed in the practice of the present inventioncomprises a polyethylene glycol (PEG) and, optionally, a wax. The polishcoat imparts an elegant, glossy sheen to tablets so coated. In additionto having utility in conjunction with the specific subcoat disclosedherein, the polish coat may generally be utilized on any coated tablet.So long as the polish coat does not adversely interact with theunderlying coating, it may be utilized. It is therefore suitable for useon tablets or other solid dosage units which bear film coated or sugarcoated layers.

[0020] Generally useful as PEG's in the formation of a polish coat arethose which readily form aqueous solutions. Generally, these are PEG'shaving molecular weights ranging from about 500 to about 50,000.Preferably, PEG's should have molecular weights ranging from about 4000to about 15,000. Most preferred in the practice of the present inventionis the use of a PEG having a molecular weight of about 8,000. ThePEG-containing polish coats are applied through spray coating technologywhich is well known in the art. The polish coat may be present inamounts such that they contribute to the weight gain of the final dosageunit from about 0.01 to about 2.0 wt. %, preferably about 0.1 to about0.5 wt. %, and most preferably about 0.25 wt. %.

[0021] The polish coat may additionally contain a wax. Preferably, theoptional wax coating is utilized. Most preferably, Carnauba wax isemployed. The wax is applied as a dusting to the dosage units to whichthe PEG-containing polish coating has been applied. The wax is presentin extremely small quantities as it is only present to impart additionalsheen to the dosage unit. Preferred is the use of the wax coating inamounts of about 0.03 wt. %.

[0022] In the practice of the present invention, an optional colorcoatmay be present. This coating serves to impart both color and additionallayers of taste-masking/degradation protection to the coated dosageunits. The colorcoat comprises a colorant and a sugar. Any colorant maybe used so long as it is compatible with the subcoat, polish coat andthe components thereof. Generally speaking, any pharmaceuticallyacceptable colorant may be used. A preferred colorant is Opadry®,available from Colorcon of West Point, Pa.

[0023] The sugar component used in the colorcoat may be the same as ordifferent from the sugar component used in the formation of the subcoat.Preferably, a polysaccharide is used as the sugar in the colorcoat. Mostpreferably, sucrose is employed. The colorcoat may also includeadditional sweeteners, flavorants, or a combination thereof. A preferredadditional sweetener is acesulfame-K.

[0024] The optional colorcoat may contain up to 60 percent by weight ofthe sugar component. Typically the colorcoat includes from about 40 toabout 60 percent by weight of colorant and from about 40 to about 60percent by weight of sugar component, based upon 100 percent by weightof the colorcoat. Preferably, the colorcoat includes about 50 percent byweight of colorant and about 50 percent by weight of sugar component, onthe same basis.

[0025] The coating system of the present invention may be used to coatpharmaceutical cores, such as, for example, cores of dosage unit formssuch as, for example, tablets or caplets.

[0026] Such cores may include a medicament, such as, for example,ibuprofen, ketoprofen, aspirin, acetaminophen, and the like. Such coresmay further comprise the typical excipients found in pharmaceuticaldosage units (e.g. disintegrants, antioxidants and sustained-releasecomponents).

[0027] The coating systems of the present invention may be applied topharmaceutical cores by methods well known to those skilled in the artsuch as spray coating. Typically, the above-described layers are appliedsequentially. Preferably, the subcoat is applied as about a 12 percentsolution and imparts about a 2 percent weight gain, based upon 100percent by weight of the core. The colorcoat, if employed, is preferablyapplied as about a 12 percent solution and imparts about a 4 percent byweight gain, based upon 100 percent by weight of the core. ThePEG-containing polish coat is preferably applied so as to impart about a0.25 percent weight gain, based upon 100 percent by weight of the core.The wax layer, if used in the final polish coat, is typically present inan amount of about 1 to about 30 weight percent of the polish coat. Thisrepresents about 0.05 to about 1.00 mg per tablet, preferably about 0.2to about 0.5 mg per tablet. It should be understood however that theabove ranges are provided for general guidance only. Differentpharmaceutical actives will require additional taste-maskingeffectiveness. Further, coating levels may be varied to impart differentdegrees of sweetness, color and polish. Further, although generally noteconomical, thicker coatings can always be applied.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0028] The following examples are intended to describe the presentinvention without limitation.

EXAMPLE 1

[0029] A coating system as described in Table 1 is prepared as follows.Weight gains expressed below are relative to the core weight. TABLE 1Subcoat  2.0% weight gain   12% solution   60% by weight of HPMC E5:E15(2:1 wt. ratio)   30% by weight of sucrose  8.8% triacetin 0.03% propylgallate  0.2% acesulfame-K  1.0% flavoring Colorcoat  4.0% weight gain  50% by weight of Opadry ® 48.8% by weight of sucrose  0.2%acesulfame-K  1.0% flavoring Polish Coat 0.25% weight gain PEG 80000.03% Carnauba wax dusting (weight gain)

[0030] (a) Preparation of Subcoat

[0031] An appropriate quantity of purified water is weighed out in astainless steel beaker. Mixing with a shaft-driven, propeller type mixersuch as a Lightnin® mixer, available from Mixing Equipment Co.,Rochester, N.Y., is initiated. Sucrose is slowly added to the water andmixed until it dissolves. HPMC E5 and HPMC E15 are slowly added to thesolution and mixed until the solution is fully hydrated with no visiblelumps. Triacetin, propyl gallate, and acesulfame-K are added to thesolution and mixed until the solution has no visible lumps.

[0032] (b) Colorcoat Preparation

[0033] An appropriate quantity of purified water is weighed out in astainless steel beaker. Mixing with a Lightnin® mixer is initiated.Sucrose is slowly added to the water and mixed until it dissolves.Opadry® Brown (Formulation No. 03B16722) is slowly added to the solutionand mixed until the solution is fully hydrated with no visible lumps.Acesulfame-K is added to the solution and mixed until the solution hasno visible lumps.

[0034] This coating system is coated onto a core of ibuprofen and adisintegrant.

EXAMPLE 2

[0035] The procedure of Example 1 is followed substituting a subcoat asdescribed in Table 2 and a colorcoat as described in Table 3. TABLE 2Subcoat Percent by weight based upon Ingredient 100% by weight ofsubcoat HPMC E5 40.0 Sucrose 30.0 HPMC E15 20.0 Triacetin 8.8 PropylGallate 0.03 Acesulfame-K 0.2 Flavoring 1.0

[0036] TABLE 3 Colorcoat Percent by weight based upon Ingredient 100% byweight of colorcoat Opadry ® Brown 50.0 Sucrose 48.8 Acesulfame-K 0.2Flavoring 1.0

[0037] All patents, publications, applications, and test methodsmentioned above are hereby incorporated by reference. Many variations ofthe present matter will suggest themselves to those skilled in the artin light of the above detailed description. All such obvious variationsare within the patented scope of the appended claims.

What is claimed is:
 1. A coating system for application to solidpharmaceutical dosage units, said system comprising: a. a subcoatcomprising (i) an water soluble cellulosic material and (ii) a sugarcomponent; and b. a polish coat comprising polyethylene glycol.
 2. Thecoating system, as defined in claim 1, wherein the cellulosic materialis selected from the group consisting of hydroxypropyl cellulose,hydroxypropyl methyl cellulose and mixtures thereof.
 3. The coatingsystem, as defined in claim 1, wherein the weight ratio of cellulosicmaterial to sugar component within the subcoat ranges from about 40:60to about 85:15 percent by weight.
 4. The coating system, as defined inclaim 1, wherein the weight ratio of cellulosic material to sugarcomponent within the subcoat ranges from about 50:50 to about 70:30percent by weight.
 5. The coating system, as defined in claim 2 whereinthe hydroxypropyl methyl cellulose is selected from the group consistingof HPMC E5, HPMC E15 and mixtures thereof.
 6. The coating system, asdefined in claim 5, wherein the weight ratio of hydroxypropyl methylcellulose to sugar component within the subcoat ranges from about 60:40to about 70:30 percent by weight.
 7. The coating system, as defined inclaim 6, wherein the weight ratio of hydroxypropyl methyl cellulose tosugar component within the subcoat is about 66:33 by weight.
 8. Thecoating system, as defined in claim 1, wherein the sugar componentcomprises a polysaccharide.
 9. The coating system, as defined in claim8, wherein the polysaccharide is sucrose.
 10. The coating system, asdefined in claim 1, wherein the polish coat comprises a polyethyleneglycol selected from those having molecular weights ranging from about500 to about 50,000, and mixtures thereof.
 11. The coating system, asdefined in claim 10, wherein the polish coat comprises a polyethyleneglycol selected from those having molecular weights ranging from about4000 to about 15,000, and mixtures thereof.
 12. The coating system, asdefined in claim 10, wherein the polish coat comprises a polyethyleneglycol having a molecular weights of about
 8000. 13. The coating system,as defined in claim 1, wherein the polish coat further comprises a waxapplied over the surface of the polyethylene glycol-containing layer.14. The coating system, as defined in claim 13 wherein the wax isCarnauba wax.
 15. The coating system, as defined in claim 14, whereinthe wax is present in amounts ranging from about 1.0 to 30 wt. percent,based upon the weight of the polish coat.
 16. The coating system, asdefined in claim 1, further comprising a colorcoat interposed betweenthe subcoat and the polish coat.
 17. The coating system, as defined inclaim 16, wherein the colorcoat comprises a colorant and at least onesugar component.
 18. The coating system, as defined in claim 17, whereinthe sugar component is a polysaccharide.
 19. The coating system, asdefined in claim 18, wherein the polysaccharide is sucrose.
 20. Thecoating system, as defined in claim 17, wherein the sugar component ispresent in amounts ranging from about 40 to about 60 weight percent ofthe colorcoat.
 21. The coating system, as defined in claim 17, whereinthe sugar component is present in amounts of about 50 weight percent ofthe colorcoat.
 22. A composition comprising (i) a pharmaceuticallyactive material, and (ii) an outer coating as defined in claim
 1. 23.The composition of claim 22 wherein the pharmaceutically active materialis selected from the group consisting of aspirin, acetaminophen,ibuprofen and ketoprofen.
 24. A method for preparing a dosage unit form,said method comprising coating a core comprising a medicament and adisintegrant with a coating system as defined in claim
 1. 25. A methodfor producing a glossy finish on a coated solid pharmaceutical dosageunit comprising applying to the surface thereof a polish coat comprisinga polyethylene glycol selected from those having molecular weightsranging from about 500 to about 50,000, and mixtures thereof.
 26. Themethod, as defined in claim 25, wherein the polish coat comprises apolyethylene glycol selected from those having molecular weights rangingfrom about 4000 to about 15,000, and mixtures thereof.
 27. The method,as defined in claim 25, wherein the polish coat comprises a polyethyleneglycol having a molecular weights of about
 8000. 28. The method, asdefined in claim 25, wherein the polish coat further comprises a waxapplied over the surface of the polyethylene glycol-containing layer.29. The method, as defined in claim 28 wherein the wax is Carnauba wax.30. The method, as defined in claim 28, wherein the wax is present inamounts ranging from about 1.0 to 30 wt. percent, based upon the weightof the polish coat.